Endometriosis is defined as the presence of endometrial cells outside of the uterine cavity. The disease affects women during their childbearing years with deleterious social, sexual and reproductive consequences. The development and maintenance of endometriosis involves the establishment and subsequent sustained growth of endometrial cells at ectopic sites, most commonly the pelvic peritoneum, following retrograde menstruation (Sampson 1927 Am. J. Obstet. Gynecol. 14, 422; Ridley & Edward 1958 Am. J. Obstet. Gynecol. 76, 783-790; Lieu & Hitchcock 1968 Br. J. Obstet. Gynecol. 93, 859-862; and Thomas & Prentice 1992 Repro. Med. Rev. 1, 21-36). Except for the influences of ovarian steroid hormones (Dizerega et al., 1980 Fertil. Steril. 33, 649-653; Bergqvist et al., 1985 Am. J. Pathol. 121, 337-341) little is known about the factors that control this disease. However, it may be that the growth of ectopic endometrial implants is influenced by angiogenic growth factors (angiogenesis being the name given to the formation of new blood vessels).
Endometriotic lesions are characterised by hyper-vascularisation both within the endometriotic tissue and in the surrounding peritoneum (Shaw, p46-47 "An atlas of endometriosis" 1993, The Parthenon publishing group; and Folkman & Shing 1992 J. Biol. Chem. 267, 10931-10934). Vascular endothelial growth factor (VEGF) is a recently characterised angiogenic protein being a potent mitogen for endothelial cells and a mediator of vessel permeability (Ferrara et al., 1992 Endocrinol. Rev. 13, 18-32). VEGF and its receptors flt and KDR, which are expressed on endothelial cells, (De Vries et al., 1992 Science 255, 989-991) have been implicated in angiogenesis in the developing embryo (Breier et al., 1992 Development 114, 521-532; Jakeman et al., 1993 Endocrinology 133, 848-859; and Millauer et al., 1993 Cell 72, 835-846) and in adult tissue undergoing profound angiogenesis such as eutopic endometrium (Chamock-Jones et al., 1993 Biol. Repro. 48, 1120-1128) and the lutenised corpus luteum (Ravindranath et al., 1992 Endocrinology 13, 254-260). In addition, its role in tumour angiogenesis is becoming well established (Shweiki et al., 1992 Nature 359, 843-848; Kim et al., 1993 Nature 362, 841-844).
The present inventors sought to determine whether VEGF and its associated receptor flt are present in endometrial tissue. In addition, they sought to determine whether other cells such as the peritoneal macrophages, whose numbers and activation status are known to be elevated in this disease (Halme et al., 1983 Am. J. Obstet. Gynecol. 145, 333-337; Olive et al., 1985 Fertil. Steril. 44, 772-777; and Halme et al., 1987 Am. J. Obstet. Gynecol. 156, 783-789), may also be involved in the pathogenesis of endometriosis through the secretion of VEGF.